Search Results (2,163)

Multivalent lectin–glycan interactions (MLGIs) are vital for viral infection, cell-cell communication and regulation of immune responses. Their structural and biophysical data are thus important, not only for providing insights into their underlying mechanisms but also for designing potent glycoconjugate therapeutics against target MLGIs. However, such information remains to be limited for some important MLGIs, significantly restricting the research progress. We have recently demonstrated that functional nanoparticles, including ∼4 nm quantum dots and varying sized gold nanoparticles (GNPs), densely glycosylated with various natural mono- and oligo- saccharides, are powerful biophysical probes for MLGIs. Using two important viral receptors, DC-SIGN and DC-SIGNR (together denoted as DC-SIGN/R hereafter), as model multimeric lectins, we have shown that α-mannose and α-manno-α-1,2-biose (abbreviated as Man and DiMan, respectively) coated GNPs not only can provide sensitive measurement of MLGI affinities but also reveal critical structural information (e.g., binding site orientation and mode) which are important for MLGI targeting. In this study, we produced mannuronic acid (ManA) coated GNPs (GNP-ManA) of two different sizes to probe the effect of glycan modification on their MLGI affinity and antiviral property. Using our recently developed GNP fluorescence quenching assay, we find that GNP-ManA binds effectively to both DC-SIGN/R and increasing the size of GNP significantly enhances their MLGI affinity. Consistent with this, increasing the GNP size also significantly enhances their ability to block DC-SIGN/R-augmented virus entry into host cells. Particularly, ManA coated 13 nm GNP potently block Ebola virus glycoprotein-driven entry into DC-SIGN/R-expressing cells with sub-nM levels of EC₅₀. Our findings suggest that GNP-ManA probes can act as a useful tool to quantify the characteristics of MLGIs, where increasing the GNP scaffold size substantially enhances their MLGI affinity and antiviral potency. Full article

Background/Objectives: In the last few decades, the dengue virus, a prevalent flavivirus, has demonstrated various epidemiological, economic, and health impacts around the world. Dengue virus serotype 2 (DENV2) plays a vital role in dengue-associated mortality. The RNA-dependent RNA polymerase (RdRp) of DENV2 is a charming druggable target owing to its crucial function in viral reproduction. In recent years, streptomycetes natural products (NPs) have attracted considerable attention as a potential source of antiviral drugs. Methods: Seeking prospective inhibitors that inhibit the DENV2 RdRp allosteric site, in silico mining of the Streptome database was executed. AutoDock4.2.6 software performance in predicting docking poses of the inspected inhibitors was initially conducted according to existing experimental data. Upon the assessed docking parameters, the Streptome database was virtually screened against DENV2 RdRp allosteric site. The streptomycetes NPs with docking scores less than the positive control (68T; calc. −35.6 kJ.mol⁻¹) were advanced for molecular dynamics simulations (MDS), and their binding affinities were computed by employing the MM/GBSA approach. Results: SDB9818 and SDB4806 unveiled superior inhibitor activities against DENV2 RdRp upon MM/GBSA//300 ns MDS than 68T with ΔG_binding values of −246.4, −242.3, and −150.6 kJ.mol⁻¹, respectively. A great consistency was found in both the energetic and structural analyses of the identified inhibitors within the DENV2 RdRp allosteric site. Furthermore, the physicochemical characteristics of the identified inhibitors demonstrated good oral bioavailability. Eventually, quantum mechanical computations were carried out to evaluate the chemical reactivity of the identified inhibitors. Conclusions: As determined by in silico computations, the identified streptomycetes NPs may act as DENV2 RdRp allosteric inhibitors and mandate further experimental assays. Full article

By 2030, millions of new cancer cases will be diagnosed, as well as millions of cancer-related deaths. Traditional drug delivery methods have limitations, so developing smart drug delivery systems (SDDs) has emerged as a promising avenue for more effective and precise cancer treatment. Nanotechnology, particularly nanomedicine, provides innovative approaches to enhance drug delivery, including the use of nanoparticles. One such type of SDD is thermosensitive nanoparticles, which respond to internal and external stimuli, such as temperature changes, to release drugs precisely at tumor sites and minimize off-target effects. On the other hand, hyperthermia is a cancer treatment mode that goes back centuries and has become popular because it can target cancer cells while sparing healthy tissue. This paper presents a comprehensive review of smart thermosensitive nanoparticles for cancer treatment, with a primary focus on organic nanoparticles. The integration of hyperthermia with temperature-sensitive nanocarriers, such as micelles, hydrogels, dendrimers, liposomes, and solid lipid nanoparticles, offers a promising approach to improving the precision and efficacy of cancer therapy. By leveraging temperature as a controlled drug release mechanism, this review highlights the potential of these innovative systems to enhance treatment outcomes while minimizing adverse side effects. Full article

Background: Hemiplegic migraine (HM) is a rare and severe subtype of migraine with a complex genetic basis. Although pathogenic variants in CACNA1A, ATP1A2, and SCN1A explain some familial cases, a significant proportion of patients remain genetically undiagnosed. Increasing evidence points to an overlap between migraine and cerebral small vessel disease (SVD), implicating vascular dysfunction in HM pathophysiology. Objective: This study aimed to identify rare or novel variants in genes associated with SVD in a cohort of patients clinically diagnosed with HM who tested negative for known familial hemiplegic migraine (FHM) pathogenic variants. Methods: We conducted a case-control association analysis of whole exome sequencing (WES) data from 184 unrelated HM patients. A targeted panel of 34 SVD-related genes was assessed. Variants were prioritised based on rarity (MAF ≤ 0.05), location (exonic/splice site), and predicted pathogenicity using in silico tools. Statistical comparisons to gnomAD’s Non-Finnish European population were made using chi-square tests. Results: Significant variants were identified in several SVD-related genes, including LRP1 (p.Thr4077Arg), COL4A1 (p.Pro54Leu), COL4A2 (p.Glu1123Gly), and TGFBR2 (p.Met148Leu and p.Ala51Pro). The LRP1 variant showed the strongest association (p < 0.001). All key variants demonstrated pathogenicity predictions in multiple computational models, implicating them in vascular dysfunction relevant to migraine mechanisms. Conclusions: This study provides new insights into the genetic architecture of hemiplegic migraine, identifying rare and potentially deleterious variants in SVD-related genes. These findings support the hypothesis that vascular and cellular maintenance pathways contribute to migraine susceptibility and may offer new targets for diagnosis and therapy. Full article

Phospholipase A1 (Ves a 1), a major toxin from Vespa affinis venom, poses significant risks to allergic individuals. Nevertheless, the epitope determinants of Ves a 1 have not been characterized. Thus, identifying its linear B-cell epitopes is crucial for understanding envenomation mechanisms. In this study, we predicted and identified B-cell epitopes EP5 and EP6 as potential candidates. EP5 formed an α-helix at the active site of Ves a 1, whereas EP6 adopted an extended loop conformation. Both synthetic peptides were synthesized and evaluated for their inhibitory effects using immune-inhibitory assays with polyclonal antibodies (pAbs) targeting both native (nVes a 1) and recombinant (rVes a 1) forms. The Ves a 1 polyclonal antibodies (pAb-nVes a 1 and pAb-Ves a 1) were produced, and their specificity binding to Ves a 1 was confirmed by Western blot. Next, ELISA inhibition assays showed that EP5 and EP6 significantly blocked pAb binding to both nVes a 1 and rVes a 1. Dot blot and Western blot assays supported these findings, particularly with stronger inhibition toward rVes a 1. Furthermore, enzymatic assays indicated that nVes a 1 and rVes a 1 retained phospholipase activity. Immunoinformatics docking showed that EP5 and EP6 specifically bind to a single-chain variable fragment antibody (scFv) targeting Naja naja PLA2. Molecular analysis revealed similar amino acid interactions to the template, suggesting effective paratope–epitope binding. These results support the potential of EP5 and EP6 for future diagnosis and therapy of V. affinis venom allergy. Full article

The agents of prion diseases have the capacity to efficiently infect susceptible hosts by peripheral routes and to project to clinical target areas of the central nervous system (CNS) via peripheral nerves. Understanding the process of prion spread from the site of infection to the CNS may allow us to identify novel therapeutic strategies. To investigate the mechanism involved in the intranerval transit of 263K scrapie prions in golden Syrian hamsters (GSHs), we transected the sciatic nerve at increasing times post-footpad injection and recorded the incubation periods as estimates of the efficiency of infection. We calculated that intranerval transit of this strain of scrapie is at least 10 times faster than previously reported and may reach 50 mm/day, similar to other neurotropic viruses. By in vivo exposure/injection of sciatic nerves to 263K infectivity, we have also shown that prion entry likely occurs via nerve terminals rather than by direct contact with the sciatic nerve. Application of this experimental approach in other forms of prion diseases could allow verification of the timing of neuroinvasion, a relevant parameter for the definition of therapeutic interventions. Full article

Glyphosate has been used for roadside weed control in southern Spain for over 40 years, and most populations of goldentop (Lamarckia aurea L.) Moench have putatively developed resistance to this active ingredient. The physiological and biochemical basis for glyphosate resistance in this weed has been investigated. Dose–response studies indicated that the resistant biotype (R) was almost 13 times more resistant to glyphosate compared to a known susceptible biotype (S). Studies of foliar glyphosate retention and ¹⁴C-glyphosate uptake/translocation showed no significant differences between both L. aurea biotypes. Basal 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) activity (µmol µg⁻¹TSP min⁻¹) showed similar values between R (0.82 ± 0.04) and S (0.75 ± 0.05) biotypes. On the other hand, the resistance factor (I₅₀R/I₅₀S) did not show a difference between the two biotypes. Therefore, it was concluded that target-site (TSR) resistance mechanisms are not involved in glyphosate resistance in this weed species. The metabolism of glyphosate to form the non-toxic metabolites aminomethylphosphonic acid (AMPA), glyoxylate, and sarcosine was greater and faster in the R compared to the S biotype; thus, glyphosate resistance is due to non-target-site resistance (NTSR) mechanisms. This paper is the first report of glyphosate resistance in L. aurea in the world. Full article

Background: Deep surgical site infections (SSIs) represent a serious complication following abdominal trauma surgery; however, comprehensive risk factor analysis in large trauma populations remains limited. Although surgical site infections are recognized as preventable complications, little is known about the specific risk factors and clinical outcomes associated with deep SSIs in trauma patients at the national level. Methods: A retrospective cohort study analyzed data from the National Trauma Data Bank from 2020–2022, including 1,198,262 trauma patients with complete demographic, injury severity, and surgical procedure data. Deep SSI development, length of hospital stay, intensive care unit utilization, duration of mechanical ventilation, discharge disposition, and in-hospital mortality were assessed. Multivariate logistic regression was used to identify independent risk factors and quantify associations between patient characteristics and deep SSI occurrence. Results: Deep SSIs occurred in 601 patients (0.05%). Affected patients were younger (median 41 vs. 54 years, p < 0.001), predominantly male (73.7% vs. 61.8%, p < 0.001), and exhibited higher injury severity scores (median 17.0 vs. 5.0, p < 0.001). Major abdominal surgery was the strongest independent predictor (OR 3.08, 95% CI: 2.21–4.23, p < 0.001), followed by injury severity score (OR 1.05, 95% CI: 1.04–1.06, p < 0.001) and ICU length of stay (OR 1.04 per day, 95% CI: 1.03–1.05, p < 0.001). Patients with deep SSIs demonstrated dramatically increased hospital stays (89.5% vs. 4.5% exceeding 21 days, p < 0.001), reduced home discharge rates (28.5% vs. 48.9%, p < 0.001), and higher mortality (4.2% vs. 1.2%, p < 0.001). Conclusions: Major abdominal surgery and injury severity are primary risk factors for deep SSIs in trauma patients, with profound impacts on clinical outcomes and healthcare resource utilization. These findings highlight the importance of targeted prevention strategies for high-risk trauma patients undergoing major abdominal procedures and emphasize the significant burden that deep SSIs place on healthcare systems. Full article

The coherency matrix serves as a valuable tool for explaining the intricate details of various terrain targets. However, a significant challenge arises when analyzing ground targets with similar scattering characteristics in polarimetric synthetic aperture radar (PolSAR) target decomposition. Specifically, the overestimation of volume scattering (OVS) introduces ambiguity in characterizing the scattering mechanism and uncertainty in deciphering the scattering mechanism of large oriented built-up areas. To address these challenges, based on the generalized five-component decomposition (G5U), we propose a hierarchical extension of the G5U method, termed ExG5U, which incorporates orientation and phase angles into the matrix rotation process. The resulting transformed coherency matrices are then subjected to a five-component decomposition framework, enhanced with four refined volume scattering models. Additionally, we have reformulated the branch conditions to facilitate more precise interpretations of scattering mechanisms. To validate the efficacy of the proposed method, we have conducted comprehensive evaluations using diverse PolSAR datasets from Gaofen-3, Radarsat-2, and ESAR, covering varying data acquisition timelines, sites, and frequency bands. The findings indicate that the ExG5U method proficiently captures the scattering characteristics of ambiguous regions and shows promising potential in mitigating OVS, ultimately facilitating a more accurate portrayal of scattering mechanisms of various terrain types. Full article

With the rapid advancement of UAV-based remote sensing and image recognition techniques, identifying environmental risk factors from aerial imagery has emerged as a focal point in intelligent inspection during the power transmission and distribution projects construction phase. The uneven spatial distribution of risk factors on construction sites, their weak texture signatures, and the inherently multi-scale nature of UAV imagery pose significant detection challenges. To address these issues, we propose a one-stage SRW-YOLO algorithm built upon the YOLOv11 framework. First, a P2-scale shallow feature detection layer is added to capture high-resolution fine details of small targets. Second, we integrate a reparameterized convolution based on channel shuffle (RCS) of a one-shot aggregation (RCS-OSA) module into the backbone and neck’s shallow layers, enhancing feature extraction while significantly reducing inference latency. Finally, a dynamic non-monotonic focusing mechanism WIoU v3 loss function is employed to reweigh low-quality annotations, thereby improving small-object localization accuracy. Experimental results demonstrate that SRW-YOLO achieves an overall precision of 80.6% and mAP of 79.1% on the State Grid dataset, and exhibits similarly superior performance on the VisDrone2019 dataset. Compared with other one-stage detectors, SRW-YOLO delivers markedly higher detection accuracy, offering critical technical support for multi-scale, heterogeneous environmental risk monitoring during the power transmission and distribution projects construction phase, and establishes the theoretical foundation for rapid and accurate inspection using UAV-based intelligent imaging. Full article

Background: Preeclampsia (PE) is a pregnancy-specific disease and hypertensive disorder with a multifactorial pathogenesis involving complex molecular regulatory networks. Recent studies highlight the critical role of non-coding RNAs, particularly miRNAs and lncRNAs, in PE development. This study investigates the molecular interaction between miR-7151-5p and the lncRNA KCNQ1OT1 and their functional contributions to PE pathogenesis. Methods: An integrative approach combining RNAhybrid-based bioinformatics, dual-luciferase reporter assays, qRT-PCR, Transwell migration and invasion assays, and RNA sequencing was employed to characterize the binding between miR-7151-5p and KCNQ1OT1 and assess their influence on trophoblast cell function and gene expression. Results: A bioinformatic analysis predicted a stable binding site between miR-7151-5p and KCNQ1OT1 (minimum free energy: –37.3 kcal/mol). The dual-luciferase reporter assay demonstrated that miR-7151-5p directly targets KCNQ1OT1, leading to suppressed transcriptional activity. In HTR8/SVneo cells, miR-7151-5p overexpression significantly downregulated both KCNQ1OT1 and Notch1 mRNA, whereas its inhibition showed no significant changes, suggesting additional regulatory mechanisms of Notch1 expression. Transwell assays indicated that miR-7151-5p overexpression suppressed trophoblast cell migration and invasion, whereas its inhibition enhanced these cellular behaviors. RNA-seq analysis further revealed that miR-7151-5p overexpression altered key signaling pathways, notably the TGF-β pathway, and significantly modulates PE-associated genes, including PLAC1, ANGPTL6, HIRA, GLA, HSF1, and BAG6. Conclusions: The regulatory effect of miR-7151-5p on KCNQ1OT1, along with its influence on trophoblast cell dynamics via Notch1 and TGF-β signaling pathways, highlights its role in PE pathogenesis and supports its potential as a biomarker in early PE screening. Full article

Many bacteria, such as Pseudomonas aeruginosa, have encoded many toxins like RhsP2 that target non-coding RNAs (ncRNAs) in a similar mechanism to ART components; bacterial RNA loses its function of amino acid translation. A virtual screening approach was used to investigate RhsP2, which targets 16s rRNAs and then disrupts the translation of bacterial amino acids to proteins. Rifamycin is the bioreference as it forms a stable complex with the bacterial RNA in its active sites. Using different docking software can determine the best predicted conformations between RhsP2/16S and rRNA, and analyzing the docking score for both Affinity Binding and the root mean square deviation (RMSD) of particle coordinates helps choose the most appropriate drugs by using tools such as bioinformatics platforms and databases. Full article

Abiotic stress can reprogram the gametophytic pathway; the mechanisms by which floral bud pre-treatment influences microspore embryogenesis initiation remain unclear. In this study, we use bisulfite sequencing, sRNA-seq, and RNA-seq to analyze the dynamic changes in rice microspores under different cold treatment durations. Our results showed that a 10-day cold treatment is essential for CXJ microspore embryogenesis initiation. DNA methylation levels showed a slight change at CG, CHG, and CHH sites under cold treatment. The number of both hyper- and hypomethylated DMRs increased over cold treatment, with more hypermethylated DMRs at 5 and 10 dpt. Hypermethylated DMRs were more frequently in the TSS region compared to hypomethylated DMRs. The proportion of 24 nt sRNAs increased upon cold stress, with more downregulated than upregulated sRNAs at 10 dpt. The number of DMR target DEGs increased from 5 to 10 dpt. Promoter hypomethylation at the CHH site was more frequently associated with DEGs. These outcomes suggested that the RdDM pathway participates in the initiation of rice ME. GO analysis indicated that DMR target DEGs at 10 dpt were enriched in responses to chemical stimuli, biological processes, and stress responses. An auxin-related gene, OsHOX28, was further identified. Its upregulation, potentially mediated by the RdDM pathway, may play a crucial role in the initiation of rice ME. This study provides more information on epigenetic mechanisms during rice ME. Full article

Goosegrass (Eleusine indica) is a major weed in Brazilian soybean, corn, and cotton systems, infesting over 60% of grain-producing areas and potentially reducing yields by more than 50%. Its competitiveness is due to its rapid emergence, fast tillering, C4 metabolism, and adaptability to various environmental conditions. A critical challenge relates to its widespread resistance to multiple herbicide modes of action, notably glyphosate and acetyl-CoA carboxylate (ACCase) inhibitors. Resistance mechanisms include 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) target-site mutations, gene amplification, reduced translocation, glyphosate detoxification, and mainly ACCase target-site mutations. This literature review summarizes the current knowledge on herbicide resistance in goosegrass and its management in Brazil, with an emphasis on integrating chemical and non-chemical strategies. Mechanical and physical controls are effective in early or local infestations but must be combined with chemical methods for lasting control. Herbicides applied post-emergence of weeds, especially systemic ACCase inhibitors and glyphosate, remain important tools, although widespread resistance limits their effectiveness. Sequential applications and mixtures with contact herbicides such as glufosinate and protoporphyrinogen oxidase (PPO) inhibitors can improve control. Pre-emergence herbicides are effective when used before or immediately after planting, with adequate soil moisture being essential for their activation and effectiveness. Given the complexity of resistance mechanisms, chemical control alone is not enough. Integrated weed management programs, combining diverse herbicides, sequential treatments, and local resistance monitoring, are essential for sustainable goosegrass management. Full article

The interaction between epigenetic mechanisms and the gut microbiome is potentially crucial for the development and maintenance of intestinal health. Lysine acetylation, an important post-translational modification, plays a complex and critical role in the epigenetic regulation of the host by the gut microbiota. However, there are currently no reports on how gut microbiota dysbiosis affects host physiology in early life through global lysine acetylation. In this study, we constructed a mouse model of gut microbiota dysbiosis using antibiotic cocktail therapy (ABX). Using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in the cecum, we analyzed the cecal lysine acetylome and proteome. As a result, we profiled the lysine acetylation landscape of the cecum and identified a total of 16,579 acetylation sites from 5218 proteins. Differentially acetylated proteins (DAPs) are involved in various metabolic pathways, including the citrate cycle (TCA cycle), butanoate metabolism, pyruvate metabolism, glycolysis/gluconeogenesis, and fatty acid biosynthesis. Moreover, both glycolysis and gluconeogenesis are significantly enriched in acetylation and protein modifications. This study aimed to provide valuable insights into the epigenetic molecular mechanisms associated with host protein acetylation as influenced by early-life gut microbiota disturbances. It reveals potential therapeutic targets for metabolic disorders linked to gut microbiota dysbiosis, thereby establishing a theoretical foundation for the clinical prevention and treatment of diseases arising from such dysbiosis. Full article